UBP12 and UBP13 deubiquitinases destabilize the CRY2 blue-light receptor to regulate growth

All organisms undergo growth, which is precisely controlled by exogenous and endogenous signals. Unchecked growth often leads to neoplasia and other developmental defects, severely affecting an organisms fitness. Light is a vital exogenous signal sensed by cryptochrome (CRY) blue light receptors to modulate growth and the circadian clock in plants and animals. Yet, how CRYs interpret light quantity to regulate growth in plants remains poorly understood. We show that UBP12 and UBP13 deubiquitinases physically interact with CRY2 in light. UBP12/13 negatively regulated CRY2 protein levels by promoting its ubiquitination and turnover to fine-tune growth. Unexpectedly, the destabilization of CRY2 by UBP12/13 is contrary to the general view that deubiquitinases stabilize proteins by preventing their degradation. Growth and development were explicitly affected in blue light when UBP12/13 was disrupted or overexpressed, indicating their role alongside CRY2. UBP12/13 also interacted and stabilized COP1, which is partially required for the turnover of CRY2. Despite decades of studies on deubiquitinases, the knowledge on how they are regulated is limited. Our study offers an insight into how exogenous signals and their receptors regulate deubiquitinase activity by protein-protein interaction. Altogether, our results provide a new module of cryptochromes and deubiquitinases in sensing and interpreting light cues to control growth at the most appropriate time.